Calcium levofolinate is the pharmacologically active (S)-isomer of leucovorin, a critical folate antagonist antidote and chemotherapy adjuvant. It counteracts toxicity of methotrexate and other dihydrofolate reductase inhibitors by providing reduced folate cofactors for one-carbon transfer reactions. Clinically, it is used for “leucovorin rescue” after high-dose methotrexate in osteosarcoma and to treat accidental folate antagonist overdose. It also enhances efficacy of 5-fluorouracil in colorectal cancer by stabilizing ternary complexes with thymidylate synthase. As a pharmaceutical intermediate, it serves as a key raw material for injectable formulations and analytical reference standards in oncology drug development.
